Grey matter OPCs are less mature and less sensitive to IFN gamma than white matter OPCs: consequences for remyelination

Dennis H Lentferink, Jacomien M Jongsma, Inge Werkman, Wia Baron*

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

32 Citaten (Scopus)
414 Downloads (Pure)

Samenvatting

Multiple sclerosis (MS) is a chronic inflammatory disease characterized by the formation of demyelinated lesions in the central nervous system. At later stages of the disease repair in the form of remyelination often fails, which leads to axonal degeneration and neurological disability. For the regeneration of myelin, oligodendrocyte progenitor cells (OPCs) have to migrate, proliferate and differentiate into remyelinating oligodendrocytes. Remyelination occurs faster and is more extensive in grey matter (GM) lesions than in white matter (WM) lesions. Here, we examined differences in neonatal OPCs from GM (gmOPCs) and WM (wmOPCs), both intrinsically and in response to environmental (injury) signals. We show that gmOPCs are less mature than wmOPCs, both on morphological and on gene-expression level. Additionally, gmOPCs proliferate more and differentiate slower than wmOPCs. When exposed to astrocyte-secreted signals wmOPC, but not gmOPC, migration decreases. In addition, wmOPCs are more sensitive to the detrimental effects of IFNγ treatment on proliferation, differentiation, and process arborisation, which is potentiated by TNFα. Our results demonstrate that OPCs from GM and WM differ both intrinsically and in response to their environment, which may contribute to the difference in remyelination efficiency between GM and WM MS lesions.

Originele taal-2English
Artikelnummer2113
Aantal pagina's15
TijdschriftScientific Reports
Volume8
Nummer van het tijdschrift1
DOI's
StatusPublished - 1-feb.-2018

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